The incidence of diabetes is increasing in a geometric fashion so that the effects of this disease, while already manifest in a significant portion of our country's population, may become a greater health problem in the near future. Diabetes is one of the leading causes of blindness, renal, cerebral, and cardiovascular disease today. New approaches in the treatment of diabetes are needed since the increased incidence of this disease makes it a major health concern. The basic goals of this application are as follows: a) to improve the techniques of isolation, investigation, and prevention of intact viable islets of Langerhans in rats, monkeys, and humans; b) to transplant these islets into streptozotocin induced diabetic animal recipients a technique which has already been successfully accomplished in the diabetic rat; c) to study the clinical, morphologic and metabolic effects of these transplanted islets in the recipient rat and monkey models as compared to normal and diabetic controls. The results of these proposed studies should provide the necessary information to determine the potential benefits of human application of these techniques and to identify and overcome complications which may be encountered. In this manner, safe and effective human trials of islet transplantation can be contemplated against the background of a comprehensive subhuman primate program.